| First Author | Altuwaijri S | Year | 2009 |
| Journal | Mol Endocrinol | Volume | 23 |
| Issue | 4 | Pages | 444-53 |
| PubMed ID | 19164450 | Mgi Jnum | J:146896 |
| Mgi Id | MGI:3838896 | Doi | 10.1210/me.2008-0106 |
| Citation | Altuwaijri S, et al. (2009) Susceptibility to autoimmunity and B cell resistance to apoptosis in mice lacking androgen receptor in B cells. Mol Endocrinol 23(4):444-53 |
| abstractText | Estrogens have been linked to a higher female incidence of autoimmune diseases. The role of androgen and the androgen receptor (AR) in autoimmune diseases, however, remains unclear. Here we report that the lack of AR in B cells in different strains of mice, namely general AR knockout, B cell-specific AR knockout, and naturally occurring testicular feminization mutation AR-mutant mice, as well as castrated wild-type mice, results in increased B cells in blood and bone marrow. Analysis of the targeted mice, together with bone marrow transplantation using Rag1(-/-) recipients, overexpression of retrovirally encoded AR-cDNA, and small interfering RNA-mediated AR mRNA knockdown approaches also show that the B cell expansion results from resistance to apoptosis and increased proliferation of bone marrow precursor B cells, accompanied by changes in several key modulators related to apoptosis, such as Fas/FasL signals, caspases-3/-8, nuclear factor-kappaB, and Bcl-2. We also show that the effects of AR loss are, in part, B cell intrinsic. Mice bearing AR-deficient B cells show increased levels of serum IgG2a and IgG3 as well as basal double-stranded DNA-IgG antibodies and are more vulnerable to development of collagen-induced arthritis. Together, these data indicate that androgen/AR play a crucial role in B cell homeostasis and tolerance. Therapies targeting AR might provide an alternative strategy with which to battle autoimmune diseases. |
